Geiger Thomas R, Peeper Daniel S
Division of Molecular Genetics, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands.
Biochim Biophys Acta. 2009 Dec;1796(2):293-308. doi: 10.1016/j.bbcan.2009.07.006. Epub 2009 Aug 14.
Metastasis, the spread of malignant cells from a primary tumor to distant sites, poses the biggest problem to cancer treatment and is the main cause of death of cancer patients. It occurs in a series of discrete steps, which have been modeled into a "metastatic cascade". In this review, we comprehensively describe the molecular and cellular mechanisms underlying the different steps, including Epithelial-Mesenchymal Transition (EMT), invasion, anoikis, angiogenesis, transport through vessels and outgrowth of secondary tumors. Furthermore, we implement recent findings that have broadened and challenged the classical view on the metastatic cascade, for example the establishment of a "premetastatic niche", the requirement of stem cell-like properties, the role of the tumor stroma and paracrine interactions of the tumor with cells in distant anatomical sites. A better understanding of the molecular processes underlying metastasis will conceivably present us with novel targets for therapeutic intervention.
转移是指恶性细胞从原发性肿瘤扩散到远处部位，这是癌症治疗面临的最大问题，也是癌症患者死亡的主要原因。它发生在一系列离散的步骤中，这些步骤已被建模为一个“转移级联”。在这篇综述中，我们全面描述了不同步骤背后的分子和细胞机制，包括上皮-间质转化（EMT）、侵袭、失巢凋亡、血管生成、通过血管运输以及继发性肿瘤的生长。此外，我们纳入了最近的研究发现，这些发现拓宽并挑战了关于转移级联的传统观点，例如“前转移微环境”的建立、干细胞样特性的需求、肿瘤基质的作用以及肿瘤与远处解剖部位细胞的旁分泌相互作用。对转移背后分子过程的更好理解有望为我们提供新的治疗干预靶点。
